Abelacimab Reduces Bleeding in AF Patients on Antiplatelet Therapy

Abelacimab (Anthos) demonstrated consistent and significant reduction in bleeding for patients on or off antiplatelet therapy (APT) compared with rivaroxaban in the AZALEA-TIMI 71 trial (NCT04755283). The data presented at the American Heart Association 2024 Scientific Sessions indicates that abelacimab is a potent anticoagulant agent available for patients with atrial fibrillation (AF) at moderate-to-high risk of stroke.¹

According to the CDC, AF is the most common type of heart arrhythmia that affects an estimated 12.2 million individuals in the United States. Patients with AF have a 5-fold risk of an ischemic stroke, which are likely to be fatal or lead to permanent neurological damage. Anticoagulants, such as rivaroxaban (Xarelto; Janssen Pharmaceutical Inc), are prescribed to reduce stroke risk and prevent blood clots; however, they come with the potential adverse effect of increased bleeding.^2,3

Abelacimab is an investigational, selective, fully human monoclonal antibody that binds tightly to factor XI, preventing the generation of the activated form, factor XIa. In the sub-study of AZALEA-TIMI 71, the agent showed significant capabilities in reducing bleeding in patients with AF.⁴

“Abelacimab targets just 1 factor in the blood clotting cascade that's very important for the bad clotting causing a heart attack or stroke, but it doesn't seem necessary for forming the blood clots that allow injured blood vessels to heal,” said Christian T. Ruff, MD, MPH, senior investigator of TIMI Group and director of general cardiology in the cardiovascular division at Brigham and Women's Hospital. "When we presented the results from the AZALEA-TIMI 71 trial a year ago, we realized the promise of factor XI inhibition with abelacimab that we reduced bleeding by 60% to 70% and that's really just a ground-breaking result.”³

The multicenter, randomized, active-controlled study evaluated the bleeding profile of abelacimab compared with rivaroxaban in over 1200 patients with a history of AF or atrial flutter with planned indefinite anticoagulation. The researchers randomized the participants in a 1:1:1 ratio to receive either abelacimab 150 mg (n = 427), abelacimab 90 mg (n = 425), or rivaroxaban 20 mg (n = 430). Abelacimab was administered subcutaneously as a monthly injection and rivaroxaban was a daily oral tablet.^4,5

According to the data, abelacimab resulted in a 67% reduction in bleeding compared with rivaroxaban (a 10.6% incidence rate for rivaroxaban to a 3.5% incidence rate for abelacimab 150 mg). The absolute rate of bleeding observed was higher when rivaroxaban was combined with antiplatelet therapy compared with rivaroxaban alone (10.6% vs. 7.7%, respectively).⁴

Regardless of APT, the rate of bleeding in patients treated with abelacimab 150 mg was similar (3.5% abelacimab with APT vs 3.1% abelacimab alone). Additionally, the absolute risk difference between abelacimab 150 mg and rivaroxaban was also greater in patients on APT compared with those not receiving APT (7.1% vs 4.6%).⁴

"Given the elevated bleeding risks associated with traditional anticoagulants, particularly when combined with antiplatelet agents, abelacimab may offer a safer alternative for patients with atrial fibrillation,” said Ruff. “These data suggest that abelacimab may potentially be an attractive option for those patients who could benefit from anticoagulation and antiplatelet therapy.”⁴

REFERENCES

1. Safety and tolerability of abelacimab (maa868) vs. rivaroxaban in patients with atrial fibrillation (azalea-timi 71). ClinicalTrials.gov Identifier: NCT04755283. Updated July 23, 2024. Accessed November 18, 2024. https://clinicaltrials.gov/study/NCT04755283

2. About atrial fibrillation. CDC. Accessed November 18, 2024. https://www.cdc.gov/heart-disease/about/atrial-fibrillation.html

3. Gerlach A. Reduced bleeding with abelacimab could transform atrial fibrillation treatment. Pharmacy Times. November 17, 2024. Accessed November 18, 2024. https://www.pharmacytimes.com/view/reduced-bleeding-with-abelacimab-could-transform-atrial-fibrillation-treatment

4. Anthos therapeutics shares new analysis from the landmark azalea-timi 71 study demonstrating the factor xi inhibitor abelacimab substantially reduced bleeding in patients on antiplatelet therapy compared to rivaroxaban. News release. Biospace. November 18, 2024. Accessed November 19, 2024. https://www.biospace.com/press-releases/anthos-therapeutics-shares-new-analysis-from-the-landmark-azalea-timi-71-study-demonstrating-the-factor-xi-inhibitor-abelacimab-substantially-reduced-bleeding-in-patients-on-antiplatelet-therapy-compared-to-rivaroxaban

5. Kumbhani D. A multicenter, randomized, active-controlled study to evaluate the safety and tolerability of two blinded doses of abelacimab compared with open-label rivaroxaban in patients with atrial fibrillation - azalea-timi 71. JACC. November 11, 2023. https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2023/11/10/22/46/azalea-timi-71